{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,27]],"date-time":"2026-10-27T16:55:12Z","timestamp":1793120112943,"version":"4.5.0"},"reference-count":119,"publisher":"MDPI AG","issue":"7","license":[{"start":{"date-parts":[[2026,6,27]],"date-time":"2026-06-27T00:00:00Z","timestamp":1782518400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Key Project of International Scientific and Technological Cooperation of Henan Province","award":["241111520400"],"award-info":[{"award-number":["241111520400"]}]},{"name":"Henan Provincial Natural Science Foundation General Program","award":["262300421517"],"award-info":[{"award-number":["262300421517"]}]},{"name":"Joint Fund of the Henan Provincial Science and Technology R&D Program","award":["252103810370"],"award-info":[{"award-number":["252103810370"]}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"crossref","award":["32300120"],"award-info":[{"award-number":["32300120"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"crossref"}]},{"award":["32300120"],"award-info":[{"award-number":["32300120"]}],"id":[{"id":"https:\/\/ror.org\/01h0zpd94","id-type":"ROR","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100013314","name":"111 Project","doi-asserted-by":"crossref","award":["D20036"],"award-info":[{"award-number":["D20036"]}],"id":[{"id":"10.13039\/501100013314","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Veterinary Sciences"],"abstract":"<jats:p>Influenza viruses continue to pose a significant threat to both animal and public health due to their rapid evolution and the frequent emergence of antiviral resistance. Host-directed antiviral (HDA) strategies, which target host factors essential for viral replication, may represent an alternative to conventional virus-targeting approaches. However, the identification of reliable and therapeutically actionable host targets remains a major challenge, primarily due to the complexity and context dependency of host\u2013virus interactions. Recent advancements in multi-omics technologies, including functional genomics, transcriptomics, and proteomics, have facilitated the systematic characterization of host factors involved in influenza virus infection. These methodologies have unveiled intricate regulatory networks that govern viral replication and host immune responses. Nonetheless, translating large-scale datasets into biologically meaningful targets necessitates robust integrative frameworks. In this context, artificial intelligence (AI) and machine learning methods offer powerful tools for data integration, target prioritization, and predictive modeling. In this Review, we summarize current insights into host factors that regulate influenza virus infection and discuss how multi-omics and AI-driven approaches are expediting host target discovery. Furthermore, we highlight the potential of these strategies to enhance antiviral development while addressing key challenges related to specificity, safety, and translational application. Collectively, these advancements lay a foundation that may support the rational design of next-generation host-directed antivirals.<\/jats:p>","DOI":"10.3390\/vetsci13070626","type":"journal-article","created":{"date-parts":[[2026,6,30]],"date-time":"2026-06-30T02:11:57Z","timestamp":1782785517000},"page":"626","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Host-Directed Antiviral Strategies Against Influenza Viruses: Host Targets, Multi-Omics Approaches and AI-Assisted Discovery"],"prefix":"10.3390","volume":"13","author":[{"given":"Xianfeng","family":"Hui","sequence":"first","affiliation":[{"name":"Department of Immunology, School of Basic Medical Sciences, Henan Medical University, Xinxiang 453003, China"},{"name":"Henan Key Laboratory of Immunology and Targeted Drug, Henan Medical University, Xinxiang 453003, China"},{"name":"Xinxiang Engineering Technology Research Center of Immune Checkpoint Drug for Liver-Intestinal Tumors, Henan Medical University, Xinxiang 453003, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shihuan","family":"Ding","sequence":"additional","affiliation":[{"name":"Department of Immunology, School of Basic Medical Sciences, Henan Medical University, Xinxiang 453003, China"},{"name":"Henan Key Laboratory of Immunology and Targeted Drug, Henan Medical University, Xinxiang 453003, China"},{"name":"Xinxiang Engineering Technology Research Center of Immune Checkpoint Drug for Liver-Intestinal Tumors, Henan Medical University, Xinxiang 453003, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shuoxiang","family":"Gao","sequence":"additional","affiliation":[{"name":"Department of Immunology, School of Basic Medical Sciences, Henan Medical University, Xinxiang 453003, China"},{"name":"Henan Key Laboratory of Immunology and Targeted Drug, Henan Medical University, Xinxiang 453003, China"},{"name":"Xinxiang Engineering Technology Research Center of Immune Checkpoint Drug for Liver-Intestinal Tumors, Henan Medical University, Xinxiang 453003, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shuochen","family":"Xu","sequence":"additional","affiliation":[{"name":"Department of Immunology, School of Basic Medical Sciences, Henan Medical University, Xinxiang 453003, China"},{"name":"Henan Key Laboratory of Immunology and Targeted Drug, Henan Medical University, Xinxiang 453003, China"},{"name":"Xinxiang Engineering Technology Research Center of Immune Checkpoint Drug for Liver-Intestinal Tumors, Henan Medical University, Xinxiang 453003, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tiesuo","family":"Zhao","sequence":"additional","affiliation":[{"name":"Department of Immunology, School of Basic Medical Sciences, Henan Medical University, Xinxiang 453003, China"},{"name":"Xinxiang Engineering Technology Research Center of Immune Checkpoint Drug for Liver-Intestinal Tumors, Henan Medical University, Xinxiang 453003, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0008-3909-7256","authenticated-orcid":false,"given":"Xiaowei","family":"Tian","sequence":"additional","affiliation":[{"name":"Xinxiang Engineering Technology Research Center of Immune Checkpoint Drug for Liver-Intestinal Tumors, Henan Medical University, Xinxiang 453003, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2454-3814","authenticated-orcid":false,"given":"Hui","family":"Wang","sequence":"additional","affiliation":[{"name":"Henan Key Laboratory of Immunology and Targeted Drug, Henan Medical University, Xinxiang 453003, China"},{"name":"Henan Collaborative Innovation Center of Molecular Diagnosis and Laboratory Medicine, School of Medical Technology, Henan Medical University, Xinxiang 453003, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,6,27]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"105","DOI":"10.1146\/annurev-virology-101416-041726","article-title":"Constraints, Drivers, and Implications of Influenza A Virus Reassortment","volume":"4","author":"Lowen","year":"2017","journal-title":"Annu. 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